Evidence favouring the Existence of a Single Adrenergic Receptor

Kunos, George; Szentiványi, M.

doi:10.1038/2171077a0

Cited by 111 publications

(37 citation statements)

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“…Recently, several workers (16)(17)(18)(19) have reported the existence of both alpha and beta receptors in the hearts of mammals. On the basis of our observations, it was concluded that alpha adrenergic receptors play some role in the inotropic effect of PHE and that PHE has both alpha and beta stimulant actions.…”

Section: Discussionmentioning

confidence: 99%

Effect of Hypothyroid Status on Myocardial Responses to Sympathomimetic Drugs

et al. 1971

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The physiological relationship between thyroid hormone and the catecholamines has been investigated for many years (1, 2). In spite of numerous studies it is still not clear whether thyroid status alters the sensitivity of the heart to catecholamines. Coville (3) has reported that thyroid hormone increased the magnitude of the response to catecholamines, while some authors have failed to show that altering the thyroid status affects the response to catecholarnines (4, 5). Recently, it was tried to explore some effects of thyroidectomy on the response of alpha and beta adrenergic receptor mechanisms to catecholamines (6). A few workers have reported the existence of both alpha and beta receptors in the hearts of mammals (7,8).
Present studies reported here were made in an attempt to clarify some of the discrepancies in many reports by seeking a quantitative difference between different types of cardiac adrenergic receptor mechanisms after 6-propyl-2-thiouracil (PTU) treatment. METHODSMale Wistar strain rats (170 to 200 g) were used for experiments. The rats were divided into two groups. Group A was served as control. Group B -,vas in a hypothyroid state produced by feeding on 0.15 % PTU diet for 6 to 8 weeks. This group developed dryness of fur, slow heart rate and a great retardation in growth.Each rat was killed by a blow on the head and the heart was rapidly removed and the left atrium dissected free. Isolated left atria were suspended in a 25-m1 tissue bath containing Ringer solution of the following composition (mM); NaCl, 158; KCI, 5.6; CaCl2, 3.6; Na HCO2, 3.6; and glucose, 15.6. The solution was maintained at a temperature of 30 -:---0.5 C and saturated with pure oxygen. The preparations were driven at a rate of 180 beats/min.through an electrode by a square wave pulse of 6 msec duration and voltage of approximately twice threshold delivered by a stimulator (Nihon Kohden MSE-3). A force displacement transducer (Nihon Kohden SB-IT) was used for measurement of isometric contractile force which was recorded by an ink writing oscillograph. A resting tension of 0.5 g was placed on each atrium. The preparations were allowed to equilibrate in Ringer solution for about 60 min. before exposing them to drugs. Drugs were dissolved before use in 0.9;V saline.The drugs used in these experiments were 1-phenylephrine hydrochloride , 1-isoproterenol

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Section: Discussionmentioning

confidence: 99%

Effect of Hypothyroid Status on Myocardial Responses to Sympathomimetic Drugs

et al. 1971

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“…Spontaneous contractions of the hearts were recorded on a smoked drum kymograph using a spring lever with a 20 x magnification. Kunos & Szentivanyi (1968) used dinitrophenol in conjunction with low temperature to reduce the metabolic rate. In the present experiments it was considered desirable to have only one variable, and so dinitrophenol was not used.…”

Section: Methodsmentioning

confidence: 99%

“…Ahlquist (1948) classified the cardiac adrenoceptors as 8-receptors, but subsequent workers have reported the existence of both a-and ,8-receptors in the hearts of mammals (Govier, Mosal, Whittington, & Broom, 1966;Wenzel & Su, 1966: Kunos & Szentivanyi, 1968;Berger & Mokler, 1969) and of frogs (Kunos & Szentivanyi, 1968). Kunos & Szentivanyi (1968), using isolated frog and rat hearts.…”

Section: Introductionmentioning

confidence: 99%

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Temperature modulation of α‐ and β‐adrenoceptors in the isolated frog heart

Buckley

Jordan

1970

British J Pharmacology

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Summary . The effects of adrenaline on the isolated frog's heart at 27° C are not antagonized by phentolamine (1·5 × 10−6m) but are abolished at 7° C. . At 27° C isoprenaline was more potent than noradrenaline, but at 7° C noradrenaline was more potent than isoprenaline. . Phenoxybenzamine (1·5 × 10−5m) or dibenamine (1·5 × 10−5m) at 7° C abolished the work output induced by adrenaline. When the temperature was raised to 24° C., adrenaline caused an increase in work output. . It is concluded that in the isolated frog heart there are at least two pools of adrenoceptors, the availability of which can be governed by temperature.

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“…As will be discussed later on, this is strong evidence against the adrenoceptor interconversion hypo-thesis proposed by Szentivanyi and Kunos (53,54,91,92). …”

Section: T 1 •mentioning

confidence: 79%

Adrenoceptors: Molecular Nature and Role in Atopic Diseases

Djurup

1981

Allergy

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Since Szentivanyi proposed the idea that asthma and other atopic ditseases are due to a P adrenergic defect there has been much interest in the role of the adrenergic receptors in allergy. The radioactive ligand binding techniques developed within the last few years have greatly increased our knowledge concerning the molecular nature of the adrenoceptors and the events following receptor sdmulation. The adrenoceptors have shown to be very dynamic structures. Their number and affinity may be altered due to various physiological and pharmacological stimuli. Their role in the pathogenesis of atopic diseases has not been definitely settled, but there seem to be a true beta adrenergic hyporesponsiveness and alpha hyperresponsiveness in asthma. This article briefly describes the radioligand binding technique and summarizes our present knowledge of the nature of the alpha and beta adrenoceptors and their possible role in atopic diseases.Key words: adrenergic receptors; atopy; asthma. Accepted fcyr publication 11 January 1981, , , rr 1 , ^^ 01 receptor is defmed as a receptor for Functional subclassification of the adrenoceptorswhich epmephrme is a more potent stimulator It has been known since the beginning of the (agonist) than norepinephrine which again is century that the sympathomimetic amines have more potent than isoproterenol. The potency both excitatory and inhibitory effects in the of the amines was examined in intact animals organism. Early investigators proposed the or isolated organ preparations. In contrast, the existence of two fundamental types of mediator P receptor is defined as a receptor for which substances: an excitatory sympathin E and an isoproterenol is a more potent agonist than inhibitory sympathin I (1). As no amine which epinephrine which again is more potent than fulfilled the requirements for either sympathin norepinephrine. The development of relatively E or I could be found, the idea of two different selective a and |3 antagonists has further conreceptor types emerged. On the basis of the firmed the pharmacological usefulness of the a relative potency of six adrenergic amines on and P receptor concept. Table 1 summarizes various biological (mainly haemodynamic) pa-the major pharmacological characteristics of rameters, Ahlquist (1) defined two different the a and the j3 receptor. receptors: an a receptor which mediates most In 1967, Lands (55) showed that there is of the adrenergic amines' excitatory functions marked similarity between the relative poten-(vasoconstriction, pupil dilation, uterine con-cies of sympathomimetic amines on lipolysis traction) and a few inhibitory (intestinal relax-and cardiac stimulation on the one hand and ation), and a P receptor which mediates most of on bronchodilation and vasodepression on the the inhibitory functions (vasodilation, broncho-other. Furthermore, a potent lipolytic and cardilation, uterine relaxation) and a few excita-diac stimulating amine is a poor bronchodilator tory (cardiac inotropy and chronotropy).and vasodepressor. Therefore, Lands s...

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Evidence favouring the Existence of a Single Adrenergic Receptor

Cited by 111 publications

References 2 publications

Effect of Hypothyroid Status on Myocardial Responses to Sympathomimetic Drugs

Effect of Hypothyroid Status on Myocardial Responses to Sympathomimetic Drugs

Temperature modulation of α‐ and β‐adrenoceptors in the isolated frog heart

Adrenoceptors: Molecular Nature and Role in Atopic Diseases

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